Profound deficits in social relationships are among the most disabling features of schizophrenia, but these symptoms are poorly responsive to existing medications and relatively little is known about their neurobiological substrates. This is the second revision of our project to explore the associations among lifelong social function and related phenomenology to olfactory threshold, odor identification, and CNS olfactory processing in 50 schizophrenia patients, 50 bipolar patients (who may not have SlD, but who may have psychosis and social deficits) and 50 healthy subjects. We have been highly responsive to the prior critique and have narrowed the proposal by removing the genetic component, streamlining the clinical assessments, and reducing the study duration to four years without curtailing the number of study subjects. Prompted by the animal literature that links olfaction with social affiliation, we identified a noteworthy association between the deficit syndrome and smell identification deficits in schizophrenia (Malaspina et al, 2002), more recently showing that a specific relationship between odor identification and social volition explained these findings (Malaspina and Coleman, 2003). The current study will extend and clarify these findings in schizophrenia, bipolar and healthy samples. We will comprehensively characterize life long and present social adjustment and olfactory capacity among rigorously diagnosed and clinically evaluated subjects and will also assess endocrine status, which may interrelate with olfaction. Using state of the art equipment and methods, we will examine the reactivity of central nervous system components to odor stimuli, by obtaining and linking behavioral, electroencephalogram (EEG), evoked response potentials (ERPs) and autonomic nervous system (ANS) responses to standard olfactory stimuli. Determining the neurocircuitry of social impairments may be a key to understanding the pathophysiology of some of the most profound disabilities in the disease. The study may also have implications for treatment, if indices derived from the clinical or electrophysiological assessment of olfactory processing turn out to be useful probes of interventions that can ameliorate social deficits. Not all schizophrenia patients have olfactory dysfunction or social deficits and we also expect to discern homogeneous subgroups within the broader diagnosis of schizophrenia. [unreadable] [unreadable]